The major goal of this project is to delineate the factors that regulate automatic activity of normal and abnormal cardiac cells and how such behavior can be modified by different cardioactive agents. It is hypothesized that patients with sinus node dysfunction have rhythm disturbances that are due to alterations of automaticity and/or conduction in the sinus node or due to prolongation of conduction time and relative refractory period of the sinoatrial junction. The hypothesis will be evaluated using the techniques of overdrive suppression, premature atrial stimulation and isoproterenol infusion in cats with sinus node dysfunction. The relation between membrane potential and automatic behavior will be determined in isolated Prukinje fiber preparations. Techniques such as rapid drive and prolonged hypothermic exposure will be used to load the inside of the fibers with Na. Thereafter the magnitude and time course of the hypepolarizaion will be recorded under control conditions and during exposure to selected cardioactive agents. Such studies will enable us to determine the mechanisms underlying distrubances of sinus node automaticity and sinoatrial conduction and to determine the possible role of the Na-K exchange pump in the regulation of cardiac automaticity and in the prevention of cardiac arrhythmias.